Neuroscience and Mental Health, Hospital for Sick Children Research Institute, Toronto, Canada; Sunnybrook Research Institute, Toronto, Canada; Division of Neuroscience, Sírio-Libanês Hospital, São Paulo, Brazil
Division of Neurosurgery, Department of Surgery, University Health Network, Toronto, Canada; Division of Neurosurgery, Department of Surgery, University of Toronto, Toronto, Canada
Gavin JB Elias
Division of Neurosurgery, Department of Surgery, University Health Network, Toronto, Canada; Division of Neurosurgery, Department of Surgery, University of Toronto, Toronto, Canada
Alexandre Boutet
Division of Neurosurgery, Department of Surgery, University Health Network, Toronto, Canada; Joint Department of Medical Imaging, University of Toronto, Toronto, Canada
Aaron Loh
Division of Neurosurgery, Department of Surgery, University Health Network, Toronto, Canada; Division of Neurosurgery, Department of Surgery, University of Toronto, Toronto, Canada
Adriana Lucia Lopez Rios
Department of Functional and Stereotactic Neurosurgery, University Hospital San Vicente Fundación, São Paulo, Brazil; Department of Functional and Stereotactic Neurosurgery, San Vicente Fundación, Barranquilla, Colombia
Cristina Torres Diaz
Department of Neurosurgery, University Hospital La Princesa, Madrid, Spain
William Omar Contreras Lopez
Nemod Research Group, Universidad Autónoma de Bucaramanga, Bucaramanga, Colombia; Division of Functional Neurosurgery, Department of Neurosurgery, FOSCAL Clinic, Bucaramanga, Colombia
Raquel Chacon Ruiz Martinez
Division of Neuroscience, Sírio-Libanês Hospital, São Paulo, Brazil; LIM 23, Institute of Psychiatry, School of Medicine, University of São Paulo, São Paulo, Brazil
Erich Talamoni Fonoff
Department of Neurology, Integrated Clinic of Neuroscience, School of Medicine, University of São Paulo, São Paulo, Brazil
Juan Carlos Benedetti-Isaac
Stereotactic and Functional Neurosurgery Division of the International Misericordia Clinic, Barranquilla, Canada
Peter Giacobbe
Sunnybrook Research Institute, Toronto, Canada; Harquail Centre for Neuromodulation, Sunnybrook Health Sciences Centre, Toronto, Canada; Department of Psychiatry, University of Toronto, Toronto, Canada
Pablo M Arango Pava
Servicio de Neuocirugia Funcional y Esterotaxia, Clinica Comuneros Bucaramanga, Clinica Desa y Clinica Dime Neurocardiovascular de Cali; Clinica Nueva del Lago, Bucaramanga, Colombia
Han Yan
Division of Neurosurgery, Department of Surgery, University of Toronto, Toronto, Canada; Division of Neurosurgery, The Hospital for Sick Children, Toronto, Canada
George M Ibrahim
Division of Neurosurgery, Department of Surgery, University of Toronto, Toronto, Canada; Division of Neurosurgery, The Hospital for Sick Children, Toronto, Canada; Institute of Biomedical Engineering, University of Toronto, Toronto, Canada; Institute of Medical Science, University of Toronto, Toronto, Canada
Nir Lipsman
Sunnybrook Research Institute, Toronto, Canada; Division of Neurosurgery, Department of Surgery, University of Toronto, Toronto, Canada; Harquail Centre for Neuromodulation, Sunnybrook Health Sciences Centre, Toronto, Canada
Andres Lozano
Division of Neurosurgery, Department of Surgery, University Health Network, Toronto, Canada; Division of Neurosurgery, Department of Surgery, University of Toronto, Toronto, Canada
Clement Hamani
Sunnybrook Research Institute, Toronto, Canada; Division of Neurosurgery, Department of Surgery, University of Toronto, Toronto, Canada; Harquail Centre for Neuromodulation, Sunnybrook Health Sciences Centre, Toronto, Canada
Deep brain stimulation targeting the posterior hypothalamus (pHyp-DBS) is being investigated as a treatment for refractory aggressive behavior, but its mechanisms of action remain elusive. We conducted an integrated imaging analysis of a large multi-centre dataset, incorporating volume of activated tissue modeling, probabilistic mapping, normative connectomics, and atlas-derived transcriptomics. Ninety-one percent of the patients responded positively to treatment, with a more striking improvement recorded in the pediatric population. Probabilistic mapping revealed an optimized surgical target within the posterior-inferior-lateral region of the posterior hypothalamic area. Normative connectomic analyses identified fiber tracts and functionally connected with brain areas associated with sensorimotor function, emotional regulation, and monoamine production. Functional connectivity between the target, periaqueductal gray and key limbic areas – together with patient age – were highly predictive of treatment outcome. Transcriptomic analysis showed that genes involved in mechanisms of aggressive behavior, neuronal communication, plasticity and neuroinflammation might underlie this functional network.
